Cytotoxic T lymphocytes (CTL) provide an important component of the host response against virally induced tumors, viruses themselves and some types of graft rejection. Using a tumor allograft model, we have been studying the mechanism by which such immune cells recognize and destroy antigen-bearing cells. We have identified unique responses within the cells being attacked which separates this form of immune damage from attack by antibody and complement (Ab + C'). Part of the current proposal is to test the hypothesis that the target itself actively participates in its own destruction after receiving a signal from the CTL. We have observed that the target response has many similarities to mitosis and therefore hypothesized that similar metabolic machinery may be involved. The current proposal seeks to extend these studies by attempting to modulate the target response using procedures which modify mitotic events in other systems. In addition, we will attempt to identify the CTL component(s) responsible for triggering the interaction. Finally, we will explore the hypothesis that some of these "mitotic" signalling events may be non-lethal and be expressed in a variety of T cell subsets. Such non-lethal signalling could be responsible for initiating damage associated with delayed type hypersensitivity reactions and produce new forms of lesions not previously associated with T cells. Some of this damage could contribute to unknown etiologies of a variety of autoimmune phenomena. Finally, we will explore potential membrane substrates of protein kinase C for their involvement in CTL function and signal transduction pathways. We have preliminary evidence for the identification of a unique peptide which is phosphorylated in response to perturbation of the T cell antigen receptor.